Ph II of Capecitabine, Carboplatin & Bevacizumab for Gastroesophageal Junction & Gastric Carcinoma

Not Recruiting

Trial ID: NCT00780494


To investigate bevacizumab in combination with carboplatin and capecitabine for patients with unresectable or metastatic GEJ or gastric cancers. We hope that by adding bevacizumab to standard chemotherapy for this patient population we will improve Progression Free Survival by 90% over historical controls.

Official Title

A Phase II Study of Capecitabine, Carboplatin, and Bevacizumab for Metastatic or Unresectable Gastroesophageal Junction and Gastric Adenocarcinoma

Stanford Investigator(s)

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine


Inclusion Criteria:

Subjects must be treated at Stanford University Medical Center for the entire length of
study participation.

   1. Patients with histologically or cytologically confirmed adenocarcinoma of the GEJ or

   2. Patients must be deemed unresectable due to involvement of critical vasculature or
   adjacent organ invasion. If unresectable, patients must show evidence of disease
   progression prior to enrollment.

   3. Patients with prior surgical resection who develop radiological or clinical evidence
   of metastatic cancer do not require separate histological or cytological confirmation
   of metastatic disease unless an interval of > 5 years has elapsed between the primary
   surgery and the development of metastatic disease. Clinicians should consider biopsy
   of lesions to establish diagnosis of metastatic disease if there is substantial
   clinical ambiguity regarding the nature or source of apparent metastases.

   4. Prior carboplatin as neoadjuvant or adjuvant therapy will be allowed if >= 6 months
   from the time of study entry.

   5. If patients use aspirin (>325mg/day) or NSAIDS at the time of enrollment, they must
   have a 10 day washout period prior to beginning protocol treatment.

   6. Low molecular weight heparin (or its equivalent, excluding warfarin) will be allowed
   for treatment of venous thromboembolic events if patients have no evidence of bleeding
   on full-dose anticoagulation.

   7. Patients must have a primary or metastatic lesion measurable in at least one dimension
   by Modified RECIST criteria (see Section 11.2.3) within 4 weeks prior to entry of

   8. Patients must have ECOG performance status of 0-1

   9. Patients must be >= 18 years of age

10. Laboratory values <= 2 weeks prior to randomization:

      - Absolute Neutrophil Count (ANC) >= 1.5 x 109/L (>= 1500/mm3)

      - Platelets (PLT) >= 100 x 109/L (>= 100,000/mm3)

      - Hemoglobin (Hgb) >= 9 g/dL

      - Serum creatinine <= 1.5 x ULN

      - Serum bilirubin <= 1.5 x ULN (<= 3.0 x ULN if liver metastases present)

      - Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) <= 3.0
      x ULN (<= 5.0 x ULN if liver metastases present). Note: ERCP or percutaneous
      stenting may be used to normalize the liver function tests.

11. Life expectancy >= 12 weeks

12. Inclusion and exclusion criteria for DCE-MRI and DWI imaging will be determined by CT
   scan as part of routine post-chemotherapy imaging. Subjects will be eligible if one
   liver metastasis is greater than 1 cm in size. Participation in the DCE-MRI and DWI
   correlate is not required for eligibility.

13. Ability to give written informed consent according to local guidelines

Exclusion Criteria:

   1. Disease-Specific Exclusions

      1. Prior chemotherapy for metastatic disease

      2. Prior full field radiotherapy <= 4 weeks or limited field radiotherapy <= 2 weeks
      prior to enrollment. Patients must have recovered from all therapy-related
      toxicities. The site of previous radiotherapy should have evidence of progressive
      disease if this is the only site of disease.

      3. Prior biologic or immunotherapy <= 2 weeks prior to registration. Patients must
      have recovered from all therapy-related toxicities

      4. Prior therapy with anti-VEGF agents

      5. If history of other primary cancer, subject eligible only if she or he has:

         - Curatively resected non-melanomatous skin cancer

         - Curatively treated cervical carcinoma in situ

         - Other primary solid tumor curatively treated with no known active disease
         present and no treatment administered for the last 3 years

      6. Concurrent use of other investigational agents and patients who have received
      investigational drugs <= 4 weeks prior to enrollment.

      7. Hypersensitivity to capecitabine, fluorouracil, or any component of the
      formulation and or a known deficiency of dihydropyrimidine dehydrogenase.

   2. General Medical Exclusions

      1. Subjects known to have chronic or active hepatitis B or C infection

      2. History of any medical or psychiatric condition or laboratory abnormality that in
      the opinion of the investigator may increase the risks associated with study
      participation or study drug administration or may interfere with the conduct of
      the study or interpretation of study results

      3. Male subject who is not willing to use adequate contraception upon enrollment
      into this study and for 6 months following the last dose of second-line treatment

      4. Female subject (of childbearing potential, post-menopausal for less than 6
      months, not surgically sterilized, or not abstinent) who is not willing to use an
      oral, patch or implanted contraceptive, double-barrier birth control, or an IUD
      during the course of the study and for 6 months following the last dose of
      second-line treatment

      5. Female subject who is breast-feeding or who has positive serum pregnancy test 72
      hours prior to randomization

      6. Pleural effusion or ascites that causes respiratory compromise (>= CTCAE grade 2

      7. Any of the following concurrent severe and/or uncontrolled medical conditions
      within 24 weeks of enrollment which could compromise participation in the study:

         - Unstable angina pectoris

         - Symptomatic congestive heart failure

         - Myocardial infarction <= 6 months prior to registration and/or randomization

         - Serious uncontrolled cardiac arrhythmia

         - Uncontrolled diabetes

         - Active or uncontrolled infection

         - Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of
         the lung.

         - Chronic renal disease

         - Acute or chronic liver disease (e.g., hepatitis, cirrhosis)

      8. Patients unwilling to or unable to comply with the protocol

      9. Life expectancy of less than 12 weeks

   10. Current, recent (within 4 weeks of the first infusion of this study), or planned
      participation in an experimental drug study other than a Genentech-sponsored
      bevacizumab cancer study

   3. Bevacizumab-Specific Exclusions

      1. Inadequately controlled hypertension (defined as systolic blood pressure >150
      and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)

      2. Any prior history of hypertensive crisis or hypertensive encephalopathy

      3. New York Heart Association (NYHA) Grade II or greater congestive heart failure
      (see Appendix A)

      4. History of myocardial infarction or unstable angina within 6 months prior to
      study enrollment

      5. History of stroke or transient ischemic attack within 6 months prior to study

      6. Known CNS disease, brain metastases.

      7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

      8. Symptomatic peripheral vascular disease

      9. Evidence of bleeding diathesis or coagulopathy

   10. Major surgical procedure, open biopsy, or significant traumatic injury within 28
      days prior to study enrollment or anticipation of need for major surgical
      procedure during the course of the study

   11. Core biopsy or other minor surgical procedure, excluding placement of a vascular
      access device, within 7 days prior to study enrollment

   12. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
      abscess within 6 months prior to study enrollment

   13. Serious, non-healing wound, ulcer, or bone fracture

   14. Urine protein >= 2+ on urinalysis dipstick and >= 1.0 gram on 24-hour urine

   15. Known hypersensitivity to any component of bevacizumab

   16. History of hemoptysis (bright red blood of ½ teaspoon or more per episode) within
      3 months prior to study enrollment.

   17. Current, ongoing treatment with full-dose warfarin.


drug: bevacizumab

drug: carboplatin

drug: capecitabine

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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